Tissue damage can result from many causes. Examples of such causes include surgical incisions, such as internal and epidermal surgical incisions; prosthetic implants, including injury attendant surgery such as hip replacements; and wounds, including lacerations, incisions, and penetrations. Often such damage is the result of herniation wherein the outer layers of the abdominal wall weaken, tear, or bulge. The resulting weakened area or hole allows for sections of the inner lining of the abdominal cavity, or peritoneum, to protrude. This protrusion can be painful and if uncorrected can result in strangulation of the protruding tissue. Although almost all tissue can become herniated, the tissue in the inguinal canal, in the navel, and surrounding the location of former incisions are most common. Since the early 1980's, the surgical techniques used in repairing inguinal or groin hernias have undergone a profound transformation. One such technique incorporates a surgically acceptable patch as part of the groin hernia repair. Goussous. (1995), “Effectiveness of The Mesh Plug Technique” (letter). Surgery; 117:600. Over time scar tissue forms around the reinforcing mesh, creating a supporting wall to minimize future hernias.
Various methods for approaching the herniated tissue and affixing the mesh prosthesis have been developed. There are two primary techniques used in hernia repair. In the traditional “open surgery” technique, the surgeon makes a three- to four-inch incision in the abdominal wall, pushes the hernial sac inside and uses mesh to reinforce the abdominal wall. The other method of hernia repair is the laparoscopic technique, wherein three tiny incisions, about the size of dime, provide the surgeon sufficient access to reposition the hernia sac back through its hole and secure a mesh patch over the weak area in the muscle wall. The incisions used in the laparoscopic technique are sufficiently small so that they can be covered by adhesive strips and there is minimal or no scarring.
The surgically acceptable patch used in both of the above-discussed techniques is generally held in place via suturing or stapling to the surrounding tissue. Unfortunately, the use of such sutures or staples may increase the patient's discomfort and increase the incidences of wound infection, vascular injury and entrapment neuropathy. While herniorrhaphies have been conducted without firmly connecting the patch to the tissue surface and allowing the pressure of the peritoneum to hold the patch against the posterior side of the abdominal wall, see Zieren et al. (1999) “Is Mesh Fixation Necessary in Abdominal Hernia Repair?” Lang. Arch Surg. 384:71-75, fixation of the patch is generally preferred in order to avoid folding, shrinkage, and migration of the patch and is usually considered to be essential in laparoscopic procedures.
Recently cyanoacrylates and fibrin glues have been used as fixatives in hernia repair. While Katkhouda et al. (2001) Ann. Surg 233:18-25 present the use of a fibrin sealant as a patch fixative, such fibrin products are made from human products and are thus susceptible to contamination. Also, fibrin adhesives are difficult to prepare and to store. The use of cyanoacrylates as adhesives also presents problems in that the adhesive may not be biocompatible and may not provide a sufficient degree of elasticity thereby resulting in increased patent discomfort and an increased incidence of reoccurrence. See, Farouk et al. (1996), “Preliminary Experience with utyl-2-Cyanoacrylate adhesive in Tension-Free Inguinal Hernia Repair,” Brit. J. Surg. 83:1100 and Jourdan et al. (1998), “The Use of N-Butyl-2-Cyanoacrylate Glue for the Fixation of Polypropylene Mesh in Laparoscopic Hernia Repair,” 6th World Cong of Endo. Surg., 1221-1225.
A new method of tissue repair has now been developed using a surgically acceptable hydrophilic-based crosslinking adhesive. The use of this adhesive composition avoids the potential complications inherent in suture or staple based methods of tissue attachment. Also, as the hydrophilic polymer-based adhesive does not contain human blood products, the danger of contamination present with fibrin adhesives is removed. While providing a stronger adhesive bond than fibrin adhesives such as TISSEEL®, the hydrophilic polymer-based crosslinking adhesive is much more flexible than cyanoacrylate adhesives and is completely biocompatible.
U.S. Pat. No. 5,162,430, to Rhee et al., and commonly owned by the assignee of the present invention, discloses collagen-synthetic polymer conjugates prepared by covalently binding collagen to synthetic hydrophilic polymers such as various derivatives of polyethylene glycol.
Commonly owned U.S. Pat. No. 5,324,775, to Rhee et al., discloses various inert, naturally occurring, biocompatible polymers (such as polysaccharides) covalently bound to synthetic, hydrophilic polyethylene glycol polymers.
Commonly owned U.S. Pat. No. 5,328,955, to Rhee et al., discloses various activated forms of polyethylene glycol and various linkages which can be used to produce collagen-synthetic polymer conjugates having a range of physical and chemical properties.
Commonly owned, U.S. application Ser. No. 08/403,358, filed Mar. 14, 1995, now abandoned, a European counterpart of which was published as EP 96102366, discloses a crosslinked biomaterial composition that is prepared using a hydrophobic crosslinking agent, or a mixture of hydrophilic and hydrophobic crosslinking agents. Preferred hydrophobic crosslinking agents include any hydrophobic polymer that contains, or can be chemically derivatized to contain, two or more succinimidyl groups.
Commonly owned U.S. Pat. No. 5,580,923 to Yeung et al., discloses a composition useful in the prevention of surgical adhesions. The composition has a substrate, which is preferably collagen and a binding agent, which preferably has at least one tissue-reactive functional group and at least one substrate-reactive functional group.
Commonly owned U.S. Pat. No. 5,614,587 to Rhee et al., discloses bioadhesive compositions having collagen crosslinked using a multifunctionally activated synthetic hydrophilic polymer, as well as methods of using such compositions to effect adhesion between a first surface and a second surface. At least one of the first and second surfaces is preferably a native tissue surface.
Japanese patent publication No. 07090241 discloses a composition used for temporary adhesion of a lens material to a machining device, which contains a mixture of polyethylene glycol, having an average molecular weight in the range of 1000-5000, and poly-N-vinylpyrrolidone, having an average molecular weight in the range of 30,000-200,000.
West and Hubbell, Biomaterials (1995) 16:1153-1156, disclose the prevention of post-operative adhesions using a photopolymerized polyethylene glycol-co-lactic acid diacrylate hydrogel and a physically crosslinked polyethylene glycol-co-polypropylene glycol hydrogel, Poloxamer 407®.
Each publication cited above and is incorporated herein by reference to describe and disclose the subject matter for which it is cited.
The invention is directed to a method of repairing tissue, such as herniated tissue, using a versatile biocompatible adhesive composition not previously disclosed or envisioned by those in the biomaterial field. The composition has a hydrophilic polymer and crosslinkable components that may be readily crosslinked upon admixture with an aqueous medium to provide a crosslinked composition suitable for use as a bioadhesive. The adhesive composition is biocompatible, and does not leave any toxic, inflammatory or immunogenic reaction products at the site of administration. Preferably, the composition is not subject to enzymatic cleavage by matrix metalloproteinases such as collagenase, and is therefore not readily degradable in vivo. As a result, the adhesive composition will degrade more slowly than either the hydrophilic polymer component or the crosslinkable component as the two components will serve to mutually protect each other from the effects of metalloproteases or hydrolysis.